Scientific Longevity Debates
Counteracting echo-chambers and dogma. Each contentious longevity dispute features the Steel-Man Standard: the strongest arguments voted on by the opposing camp as the fairest representation of their counterpart’s scientific position.
Rapamycin Dosing: Weekly Pulsed Dosing vs. Continuous Low-Dose Inhibition
Should rapamycin for longevity be administered as a single weekly bolus (5-8mg once per week) to maximize peak mTORC1 inhibition while allowing mTORC2 to recover, or does lower continuous micro-dosing provide steadier autophagy?
Metformin: Essential Geroprotector or Blunter of Exercise Adaptations?
Given evidence that metformin attenuates VO2 max and mitochondrial adaptations to aerobic exercise in healthy adults, should non-diabetics who already exercise take metformin for longevity?
NAD+ Augmentation: Nicotinamide Mononucleotide (NMN) vs. Nicotinamide Riboside (NR)
Both NMN and NR effectively raise circulating and tissue NAD+ levels, but intense debate surrounds whether NMN is directly imported via the Slc12a8 transporter or dephosphorylated extracellularly into NR prior to cell entry.
Dietary Protein Intake: Sarcopenia Defense (1.6-2.2g/kg) vs. mTOR Longevity Suppression (0.8g/kg)
Should longevity protocols prescribe high dietary protein to maximize skeletal muscle preservation and prevent frailty, or should protein (specifically leucine and methionine) be restricted to avoid chronic mTORC1 stimulation and accelerated biological aging?
GH / IGF-1 Secretagogues: Tissue Regeneration vs. Oncogenic Proliferation Risk
Growth hormone secretagogues (such as Sermorelin, Ipamorelin, and CJC-1295) restore youthful GH pulsatility and accelerate tissue repair, but elevating systemic IGF-1 may accelerate neoplastic transformation and shorten longevity.
Resveratrol: SIRT1 Longevity Activator or Overhyped PAINS Artifact?
Once heralded as the premier red-wine polyphenol that activates sirtuins and mimics caloric restriction, resveratrol is now intensely contested regarding in vivo bioavailability, off-target fluorescence artifacts, and failure in non-obese human trials.